Evolution of Salmonella O antigen variation by interspecific gene transfer on a large scale

1993 ◽  
Vol 9 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Peter Reeves
Keyword(s):  
Gene Transfer ◽  
Large Scale ◽  
O Antigen ◽  
Interspecific Gene Transfer

scholarly journals Systematic Detection of Large-Scale Multi-Gene Horizontal Transfer in Prokaryotes

2021 ◽  
Author(s):  
Lina Kloub ◽  
Sean Gosselin ◽  
Matthew Fullmer ◽  
Joerg Graf ◽  
J Peter Gogarten ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Large Scale ◽  
Single Gene ◽  
Gene Families ◽  
Microbial Evolution ◽  
Phylogenetic Distance ◽  
Secretion Systems ◽  
Type Iii Secretion Systems ◽  
A Genome ◽  
Conserved Gene

Abstract Horizontal gene transfer (HGT) is central to prokaryotic evolution. However, little is known about the “scale” of individual HGT events. In this work, we introduce the first computational framework to help answer the following fundamental question: How often does more than one gene get horizontally transferred in a single HGT event? Our method, called HoMer, uses phylogenetic reconciliation to infer single-gene HGT events across a given set of species/strains, employs several techniques to account for inference error and uncertainty, combines that information with gene order information from extant genomes, and uses statistical analysis to identify candidate horizontal multi-gene transfers (HMGTs) in both extant and ancestral species/strains. HoMer is highly scalable and can be easily used to infer HMGTs across hundreds of genomes. We apply HoMer to a genome-scale dataset of over 22000 gene families from 103 Aeromonas genomes and identify a large number of plausible HMGTs of various scales at both small and large phylogenetic distances. Analysis of these HMGTs reveals interesting relationships between gene function, phylogenetic distance, and frequency of multi-gene transfer. Among other insights, we find that (i) the observed relative frequency of HMGT increases as divergence between genomes increases, (ii) HMGTs often have conserved gene functions, and (iii) rare genes are frequently acquired through HMGT. We also analyze in detail HMGTs involving the zonula occludens toxin and type III secretion systems. By enabling the systematic inference of HMGTs on a large scale, HoMer will facilitate a more accurate and more complete understanding of HGT and microbial evolution.

scholarly journals Human peripheral blood hematopoietic progenitors are optimal targets of retroviral-mediated gene transfer

Blood ◽  
1992 ◽  
Vol 80 (6) ◽  
pp. 1418-1422 ◽  
Author(s):  
M Bregni ◽  
M Magni ◽  
S Siena ◽  
M Di Nicola ◽  
G Bonadonna ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Cancer Patients ◽  
Resistance Gene ◽  
Peripheral Blood ◽  
Large Scale ◽  
Human Peripheral Blood ◽  
High Dose ◽  
Hematopoietic Progenitors ◽  
Hematopoietic Stem

Abstract Hematopoietic progenitor cells circulate in the peripheral blood (PB) of cancer patients during the recovery phase that follows treatment with high-dose cyclophosphamide followed by hematopoietic growth factor infusion. We report that when PB progenitors were exposed in vitro to filtered supernatant from cell line PA317-N2, producing amphotropic helper-free N2 vector at conventional titers, successful retroviral- mediated transfer of neomycin resistance gene was documented by polymerase chain reaction in 93% of day 14 myelomonocytic colonies. Under the same conditions, gene transfer was achieved in 22% of steady- state bone marrow-derived myelomonocytic colonies. Neo-resistance gene transfer was documented also in a CD34+/cyclophosphamide-resistant precursor to granulocyte-macrophage colonies, an undifferentiated progenitor close to the hematopoietic stem cell. Neither cocultivation with vector-producing cells nor high vector titer were stringent requisites for efficient gene transfer. The large-scale availability of PB hematopoietic progenitors in cancer patients, together with the high gene transfer rate achieved under safe and clinically feasible conditions, support an optimal approach for gene transfer procedures into the human hematopoietic system.

scholarly journals Nanomedicine for Gene Delivery for the Treatment of Cardiovascular Diseases

2019 ◽  
Vol 19 (1) ◽  
pp. 20-30 ◽  
Author(s):  
Cen Yan ◽  
Xiao-Jiang Quan ◽  
Ying-Mei Feng
Keyword(s):  
Gene Transfer ◽  
Gene Delivery ◽  
Dna Sequences ◽  
Large Scale ◽  
Heart Function ◽  
Current Status ◽  
Future Perspective ◽  
Scale Production ◽  
Large Scale Production ◽  
Target Molecules

Background: Myocardial infarction (MI) is the most severe ischemic heart disease and directly leads to heart failure till death. Target molecules have been identified in the event of MI including increasing angiogenesis, promoting cardiomyocyte survival, improving heart function and restraining inflammation and myocyte activation and subsequent fibrosis. All of which are substantial in cardiomyocyte protection and preservation of cardiac function. Methodology: To modulate target molecule expression, virus and non-virus-mediated gene transfer have been investigated. Despite successful in animal models of MI, virus-mediated gene transfer is hampered by poor targeting efficiency, low packaging capacity for large DNA sequences, immunogenicity induced by virus and random integration into the human genome. Discussion: Nanoparticles could be synthesized and equipped on purpose for large-scale production. They are relatively small in size and do not incorporate into the genome. They could carry DNA and drug within the same transfer. All of these properties make them an alternative strategy for gene transfer. In the review, we first introduce the pathological progression of MI. After concise discussion on the current status of virus-mediated gene therapy in treating MI, we overview the history and development of nanoparticle-based gene delivery system. We point out the limitations and future perspective in the field of nanoparticle vehicle. Conclusion: Ultimately, we hope that this review could help to better understand how far we are with nanoparticle-facilitated gene transfer strategy and what obstacles we need to solve for utilization of nanomedicine in the treatment of MI.

Antimicrobial resistance: its emergence and transmission

2008 ◽  
Vol 9 (2) ◽  
pp. 115-126 ◽  
Author(s):  
Patrick Boerlin ◽  
Richard J. Reid-Smith
Keyword(s):  
Gene Transfer ◽  
Antimicrobial Resistance ◽  
Horizontal Gene Transfer ◽  
Dna Sequencing ◽  
Large Scale ◽  
Mutant Selection ◽  
The Past ◽  
New Concepts ◽  
Selection Window ◽  
Integrative Conjugative Elements

AbstractNew concepts have emerged in the past few years that help us to better understand the emergence and spread of antimicrobial resistance (AMR). These include, among others, the discovery of the mutator state and the concept of mutant selection window for resistances emerging primarily through mutations in existing genes. Our understanding of horizontal gene transfer has also evolved significantly in the past few years, and important new mechanisms of AMR transfer have been discovered, including, among others, integrative conjugative elements and ISCR(insertionsequences withcommonregions) elements. Simultaneously, large-scale studies have helped us to start comprehending the immense and yet untapped reservoir of both AMR genes and mobile genetic elements present in the environment. Finally, new PCR- and DNA sequencing-based techniques are being developed that will allow us to better understand the epidemiology of classical vectors of AMR genes, such as plasmids, and to monitor them in a more global and systematic way.

scholarly journals Extensive Phenotypic Changes Associated with Large-scale Horizontal Gene Transfer

2013 ◽  
Author(s):  
Kevin Dougherty ◽  
Brian A Smith ◽  
Autum F Moore ◽  
Shannon Maitland ◽  
Chris Fanger ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Horizontal Transfer ◽  
Large Scale ◽  
Pseudomonas Stutzeri ◽  
Transfer Event ◽  
Small Plasmid ◽  
Phenotypic Changes ◽  
Evolutionary Trajectories ◽  
Evolutionary Consequences

Horizontal gene transfer often leads to phenotypic changes within recipient organisms independent of any immediate evolutionary benefits. While secondary phenotypic effects of horizontal transfer (i.e. changes in growth rates) have been demonstrated and studied across a variety of systems using relatively small plasmid and phage, little is known about how size of the acquired region affects the magnitude or number of such costs. Here we describe an amazing breadth of phenotypic changes which occur after a large-scale horizontal transfer event (~1Mb megaplasmid) within Pseudomonas stutzeri including sensitization to various stresses as well as changes in bacterial behavior. These results highlight the power of horizontal transfer to shift pleiotropic relationships and cellular networks within bacterial genomes. They also provide an important context for how secondary effects of transfer can bias evolutionary trajectories and interactions between species. Lastly, these results and system provide a foundation to investigate evolutionary consequences in real time as newly acquired regions are ameliorated and integrated into new genomic contexts.

scholarly journals Identification of the Pseudomonas aeruginosa O17 and O15 O-Specific Antigen Biosynthesis Loci Reveals an ABC Transporter-Dependent Synthesis Pathway and Mechanisms of Genetic Diversity

2020 ◽  
Vol 202 (19) ◽  
Author(s):  
Steven M. Huszczynski ◽  
Youai Hao ◽  
Joseph S. Lam ◽  
Cezar M. Khursigara
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Abc Transporter ◽  
Specific Antigen ◽  
Opportunistic Pathogen ◽  
Content Type ◽  
O Antigen ◽  
O Antigens ◽  
Dependent Pathway

ABSTRACT Many bacterial cell surface glycans, such as the O antigen component of lipopolysaccharide (LPS), are produced via the so-called Wzx/Wzy- or ABC transporter-dependent pathways. O antigens are highly diverse polysaccharides that protect bacteria from their environment and engage in important host-pathogen interactions. The specific structure and composition of O antigens are the basis of classifying bacteria into O serotypes. In the opportunistic pathogen Pseudomonas aeruginosa, there are currently 20 known O-specific antigen (OSA) structures. The clusters of genes responsible for 18 of these O antigens have been identified, all of which follow the Wzx/Wzy-dependent pathway and are located at a common locus. In this study, we located the two unidentified O antigen biosynthesis clusters responsible for the synthesis of the O15 and the O17 OSA structures by analyzing published whole-genome sequence data. Intriguingly, these clusters were found outside the conserved OSA biosynthesis locus and were likely acquired through multiple horizontal gene transfer events. Based on data from knockout and overexpression studies, we determined that the synthesis of these O antigens follows an ABC transporter-dependent rather than a Wzx/Wzy-dependent pathway. In addition, we collected evidence to show that the O15 and O17 polysaccharide chain lengths are regulated by molecular rulers with distinct and variable domain architectures. The findings in this report are critical for a comprehensive understanding of O antigen biosynthesis in P. aeruginosa and provide a framework for future studies. IMPORTANCE P. aeruginosa is a problematic opportunistic pathogen that causes diseases in those with compromised host defenses, such as those suffering from cystic fibrosis. This bacterium produces a number of virulence factors, including a serotype-specific O antigen. Here, we identified and characterized the gene clusters that produce the O15 and O17 O antigens and show that they utilize a pathway for synthesis that is distinct from that of the 18 other known serotypes. We also provide evidence that these clusters have acquired mutations in specific biosynthesis genes and have undergone extensive horizontal gene transfer within the P. aeruginosa population. These findings expand on our understanding of O antigen biosynthesis in Gram-negative bacteria and the mechanisms that drive O antigen diversity.

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